tbuckley/cabot-search huggingface dataset:
Choroid Plexus–Infiltrating T Cells as Drivers of Murine Neuropsychiatric Lupus
Authors: Erica Moore, Michelle W. Huang, Cara A. Reynolds, Fernando Macian, Chaim Putterman
Journal: Arthritis & Rheumatology (2022)

Objective T cells are critical in the pathogenesis of systemic lupus erythematosus (SLE) in that they secrete inflammatory cytokines, help autoantibody production, and form autoreactive memory T cells. Although the contribution of T cells to several forms of organ‐mediated damage in SLE has been previously demonstrated, the role of T cells in neuropsychiatric SLE (NPSLE), which involves diffuse central nervous system manifestations and is observed in 20–40% of SLE patients, is not known. Therefore, we conducted this study to evaluate how behavioral deficits are altered after depletion or transfer of T cells, to directly assess the role of T cells in NPSLE. Methods MRL/ lpr mice, an NPSLE mouse model, were either systemically depleted of CD4+ T cells or intracerebroventricularly injected with choroid plexus (CP)–infiltrating T cells and subsequently evaluated for alterations in neuropsychiatric manifestations. Our study end points included evaluation of systemic disease and assessment of central nervous system changes. Results Systemic depletion of CD4+ T cells ameliorated systemic disease and cognitive deficits. Intracerebroventricular injection of CP–infiltrating T cells exacerbated depressive‐like behavior and worsened cognition in recipient mice compared with mice who received injection of splenic lupus T cells or phosphate buffered saline. Moreover, we observed enhanced activation in CP–infiltrating T cells when cocultured with brain lysate–pulsed dendritic cells in comparison to the activation levels observed in cocultures with splenic T cells. Conclusion T cells, and more specifically CP–infiltrating antigen‐specific T cells, contributed to the pathogenesis of NPSLE in mice, indicating that, in the development of more targeted treatments for NPSLE, modulation of T cells may represent a potential therapeutic strategy.
LGG-63 MEK inhibitor-associated retinopathy (MEKAR) in a pediatric patient with an optic pathway glioma
Authors: Anne Bendel, Mary Skrypek, Heather Johnson, Jonathan Pribila
Journal: Neuro-Oncology (2022)

Abstract Pediatric low-grade glioma (LGG) and plexiform neurofibroma (PN) universally have up-regulation of the RAS-mitogen-activated protein kinase (MAPK) pathway. Recent phase I and II clinical trials evaluating MEK inhibitors for the treatment pediatric LGG and PN report efficacy and tolerable side effects, including no reported ophthalmologic toxicity. Contrary to the pediatric experience, adult trials using MEK inhibitors describe several ophthalmologic side effects, including MEK inhibitor-associated retinopathy (MEKAR), also termed central serous-like retinopathy. MEKAR is defined as accumulation of subretinal fluid. It occurs in up to 90% of adults on MEK inhibitors, usually causing minimal to no symptoms, and typically resolving without MEK inhibitor dose adjustment. We report a case of MEKAR in a 15 year old boy with an optic pathway pilocytic astrocytoma with duplication of BRAF (7q34). Baseline ophthalmic exam showed 20/20 vision in his right eye with loss of the temporal hemifield and no light perception vision in the left eye. Nine months into treatment with Selumetinib his ophthalmologic exam and optical coherence tomography (OCT) showed asymptomatic bilateral subretinal fluid. Selumetinib was held for 2 weeks resulting in resolution of the subretinal fluid. Selumetib was resumed at the prior dose and MEKAR recurred 2 weeks later but then permanently resolved 4 weeks later despite remaining on Selumetib. Review of the literature discovered a single publication of 2 pediatric patients with optic pathway glioma who developed MEKAR around 6-7 months after initiating Selumetinib, which resolved after stopping Selumetinib. One patient was symptomatic and despite resolution of symptoms, Selumetinib was not resumed. The other patient was asymptomatic and resumed Selumetib, but redeveloped MEKAR 8 months after restarting Selumetinib. Based on adult experience and the limited pediatric experience outlined above, we recommend pediatric patients with asymptomatic and mild-moderate symptomatic MEKAR undergo close monitoring without Selumetinib dose interruption or modification unless symptoms progress.
Characterization of molecular subtypes of melanoma and development of prognostic and immunotherapy-related genetic characteristics by ferroptosis gene analysis.
Authors: Libin Xu, Tianhao Mu, Weiyu Wang, Sheng Ji Yu, Yu Zhang, Ting Liu, Wang Luqiang, Zhenguo Zhao, Zhang Xinxin, Li Xiaoyang, Wence Wu
Journal: Journal of Clinical Oncology (2022)

e21508 Background: The heterogeneity is a major problem in clinical treatment of skin cutaneous melanoma (SKCM). Objective and reproducible classification systems may help decode SKCM heterogeneity. Methods: Based on ferroptosis-related genes, this study used unsupervised clustering to identify two molecular subtypes of SKCM C1 and C2. A ferroptosis-related prognosis risk score (FPRS) model was constructed through analyzing the differences between C1 and C2 subtypes. Results: C1 showed a poor prognosis, with low infiltration degree of immune cells and TIED score were lower and higher homologous recombination defects, fraction altered, number of segments and copy number amplification and deletion. These characteristics of C2 were the opposite of C1. SKCM patients were divided into two risk groups based on FPRS. There were significant differences in the infiltration and proportion of immune cells, expression of immune checkpoint genes, and response to immune checkpoint therapy and sensitivity to chemotherapeutic drugs between high-risk group and low-risk group. Conclusions: In summary, we have identified two subtypes of SKCM with different molecular and immune characteristics based on ferroptosis-related genes, further developed and verified a FPRS model, which can be used as an independent prognostic indicator for SKCM. This study may provide a new insight for the development of personalized management of patients with SKCM.
UN Reports New Insights on Link Between Climate Change and Human Health
Authors: Melissa Suran
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
MEDB-74. Serial assessment of measurable residual disease in medulloblastoma liquid biopsies
Authors: Paul Northcott, Kyle Smith, Rahul Kumar, Leena Paul, Laure Bihannic, Tong Lin, Kendra Maass, Kristian Pajtler, Murali Chintagumpala, Jack Su, Eric Bouffet, Michael Fisher, Sridharan Gururangan, Richard Cohn, Tim Hassall, Jordan Hansford, Paul Klimo, Frederick Boop, Clinton Stewart, Julie Harreld, Thomas Merchant, Ruth Tatevossian, Geoffrey Neale, Matthew Lear, Jeffery Klco, Brent Orr, David Ellison, Richard Gilbertson, Arzu Onar-Thomas, Amar Gajjar, Giles Robinson
Journal: Neuro-Oncology (2022)

Abstract Nearly one-third of children with medulloblastoma, a malignant embryonal tumor of the cerebellum, succumb to their disease. Conventional response monitoring by imaging and cerebrospinal fluid (CSF) cytology remains challenging and a marker for measurable residual disease (MRD) is lacking. Here, we show the clinical utility of CSF-derived cell-free DNA (cfDNA) as a biomarker of MRD in serial samples collected from children with medulloblastoma (123 patients, 476 samples) enrolled on a prospective trial. Using low-coverage whole-genome sequencing, tumor-associated copy-number variations (CNVs) in CSF-derived cfDNA are investigated as an MRD surrogate. MRD is detected at baseline in 85% and 54% of patients with metastatic and localized disease, respectively. The number of MRD-positive patients decline with therapy, yet those with persistent MRD have significantly higher risk of progression. Importantly, MRD detection precedes radiographic progression in half who relapse. Our findings advocate for the prospective assessment of CSF-derived liquid biopsies in future trials for medulloblastoma.
Prevalence and survival of TNBC patients vs non-TNBC patients in India: A multi-centric real-world experience based study.
Authors: Basavalinga Sadasivaiah Ajaikumar, Roshini Das Gupta, Anisha Raju, Girdhar Verma, Anuj Gupta
Journal: Journal of Clinical Oncology (2022)

e13064 Background: Triple-Negative Breast cancer (TNBC) is a highly aggressive form of breast cancer, characterized by the lack of expression of Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal Growth Factor-2 (HER-2). Patients with TNBC do not benefit from hormonal or Trastuzumab therapy due to the lack of appropriate targets for these drugs. The current retrospective multicentric hospital-based study at HCG, India, aims to analyze the available treatment paradigms in TNBC patients in real-world evidence. Methods: Data from 3180 female breast cancer patients was collected and compiled from various medical records department (MRD) and hospital database from three HCG centers. The data comprised demographic and clinicopathological details, treatment details and survival information. In addition, the clinical and pathological parameters and survival outcomes were compared between TNBC and non-TNBC patients. Results: About 22.92% (729/3180) patients had TNBC, and 77.08% (2451/3180) patients had designated as non-TNBC. In the TNBC subgroup, 22.36% (163/729) patients belonged to the younger age group (&lt; 40 years), 65.98% (481/729) patients were in the 41-65 age group, while 11.66% (85/729) patients were &gt; 65 years old. Whereas the age-wise distribution in the non-TNBC group was as follows: &lt; 40 years- 15.46% (379/2451) patients, 41-65 years- 70.34% (1724/2451) patients, and &gt; 65 years- 14.2% (348/2451) patients. In the present cohort, TNBC and non-TNBC groups' mean age was 51.06 ± 12.15 years and 53.29 ± 11.55 years, with no statistical significance. About 11.8% (86/729) of patients in the TNBC group and 10.4% (255/2451) of patients in the non-TNBC group opted for neo-adjuvant chemotherapy. About 32.37% of patients in TNBC and 37.45% of patients in the non-TNBC group underwent surgery. The 5-year OS was 68.58% and 83.41% for TNBC and non-TNBC patients, respectively, with a median 5-year survival of 2.13 years (95% CI 2.528-3.204) for TNBC patients whereas 5-year median survival of 2.096 (95% CI 1.36-4.368). The mean survival in TNBC patients &lt; 40 years was 10.14 years, which was significantly lower when compared to patients in the 41-65 years (14.12 years) and &gt; 65 years (19.45 years). Also, patients in the TNBC group who underwent surgery had a higher mean survival of 16.72 years than those who did not opt for surgery (14.49 years). Further, chemotherapy and radiotherapy also increased the life expectancy in patients in both the TNBC and non-TNBC groups. Conclusions: In the present study cohort, TNBC distribution in the at the HCG center in the Indian subcontinent is similar to that of the western population (23% in the US and the UK). Adjuvant chemotherapy and radiotherapy were significantly higher among TNBC cases than non-TNBC cases. Lack of patient consent or proper patient follow-up further reduces survival
Impact of neuroendocrine tumor diagnosis (NET) on quality of life.
Authors: Arya Mariam Roy, Jasmine Kaur, Renuka V. Iyer
Journal: Journal of Clinical Oncology (2022)

e18614 Background: With longer median survival for NET patients, the impact of symptoms and treatments on QOL and financial well-being throughout the disease course need to be evaluated to understand the true burden of the disease on patients. Current HRQOL data are during active treatments and this prospective biobank was established to capture this information throughout the disease course. Methods: At Roswell Park Comprehensive Cancer Center, with Institutional Review Board (IRB) approval a NET biobank was established in April 2019 for collecting clinical tissue samples, patient demographics, treatment outcomes, access to care and self-reported HRQoL outcomes. Using previously developed HRQoL questionnaires, we examined the impact of the NET on the quality of life of NET patients and data of 144 patients enrolled to date in the biobank is presented here. Linear regression was used to assess the association of baseline characters with QoL variables. The analysis was done with STATA/IC 16.0. Results: A total of 144 patients are enrolled. Males were 27% (n = 39) and females were 73% (n = 105). The mean age of diagnosis was 54 +/- 0.79, with those between 45 to 65 (72%, n = 103). These patients were enrolled through support groups and social media from 30 different states in the US (135) and 9 pts from Canada. After the diagnosis, 27% of patients had to quit their job. Impact on major HRQoL variables are summarized in Table. Only 21% of patients reported that they feel knowledgeable about NET and got the majority of their support from their primary care (60%) and oncologist (57%). When asked about the most pressing need from their care team, 57% of patients requested their care team had more information about available clinical trials. Sex, age groups did not have statistically significant association on the impact of NETs on the HRQoL of patients. Conclusions: NET diagnosis affects the HRQoL of patients including their social, emotional, and financial well-being. A national biobank capturing data on various demographic, risk factors, treatment sequence, symptoms, HRQoL parameters, financial toxicity is a valuable resource to better understand the needs of this patient group.[Table: see text]
Checkpoint inhibitor and multireceptor tyrosine kinase inhibitor combination in relapsed refractory sarcomas: A single institution series.
Authors: Nupur Mittal, Brian Seyboth, Paul Kent
Journal: Journal of Clinical Oncology (2022)

11529 Background: Adolescent and young adults (AYA) with primary metastatic and relapsed bone and soft tissue sarcomas (BST) have poor prognosis with progression free survival (PFS) rates &lt; 15% and overall survival (OS) &lt; 20%. These outcomes have not improved in the past three decades, highlighting the need for new treatment paradigms. Immunotherapy is effective for multiple malignancies via blockade of CTLA4 or PD-L1 by immune checkpoint inhibitors (CPI), like nivolumab (NIVO). Sarcomas often express PD-L1 as part of their complex pathogenic pathway. Additionally, combination with oral targeted therapies is an emerging strategy for adult malignancies. Encouraging early phase results with multi-tyrosine kinase inhibitors (TKI) of several pathogenic sarcoma pathways – including lenvatinib (LEN), cabozantinib (CABO), and pazopanib – have prompted our team to offer CPI in combination with a TKI for BST patients without chemotherapy options. Methods: Retrospectively identified AYA patients with relapsed heavily pre-treated BST who received CPI/TKI combination at our institution between January 2018 to date. Results: This is the first reported series of prolonged survival in metastatic and multiply relapsed BST with CPI and TKI therapy. Table summarizes the demographics, disease features, and survival for all patients. The regimen was well tolerated in all patients, except for a rash (n = 1) that resolved by reducing the CABO dose by 25%. All patients had previously been offered palliative care before this regimen. Conclusions: Our preliminary experience with CPI/TKI combination in multiply relapsed BST shows a PFS exceeding prior PFS periods with other therapies for all patients. The overall survival is more than historical controls for initial metastatic ASPS, initial metastatic EWS, and recurrent metastatic OST. Our report will inform colleagues about the potential of CPI/TKI combination for these patients with few options. [Table: see text]
Ventilation Improvement Strategies Among K–12 Public Schools — The National School COVID-19 Prevention Study, United States, February 14–March 27, 2022
Authors: Sanjana Pampati, Catherine N. Rasberry, Luke McConnell, Zach Timpe, Sarah Lee, Patricia Spencer, Shamia Moore, Kenneth R. Mead, Colleen Crittenden Murray, Xiaoyi Deng, Ronaldo Iachan, Tasneem Tripathi, Stephen B. Martin, Lisa C. Barrios
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Effective COVID-19 prevention in kindergarten through grade 12 (K-12) schools requires multicomponent prevention strategies in school buildings and school-based transportation, including improving ventilation (1). Improved ventilation can reduce the concentration of infectious aerosols and duration of potential exposures (2,3), is linked to lower COVID-19 incidence (4), and can offer other health-related benefits (e.g., better measures of respiratory health, such as reduced allergy symptoms) (5). Whereas ambient wind currents effectively dissipate SARS-CoV-2 (the virus that causes COVID-19) outdoors,* ventilation systems provide protective airflow and filtration indoors (6). CDC examined reported ventilation improvement strategies among a nationally representative sample of K-12 public schools in the United States using wave 4 (February 14-March 27, 2022) data from the National School COVID-19 Prevention Study (NSCPS) (420 schools), a web-based survey administered to school-level administrators beginning in summer 2021.† The most frequently reported ventilation improvement strategies were lower-cost strategies, including relocating activities outdoors (73.6%), inspecting and validating existing heating, ventilation and air conditioning (HVAC) systems (70.5%), and opening doors (67.3%) or windows (67.2%) when safe to do so. A smaller proportion of schools reported more resource-intensive strategies such as replacing or upgrading HVAC systems (38.5%) or using high-efficiency particulate air (HEPA) filtration systems in classrooms (28.2%) or eating areas (29.8%). Rural and mid-poverty-level schools were less likely to report several resource-intensive strategies. For example, rural schools were less likely to use portable HEPA filtration systems in classrooms (15.6%) than were city (37.7%) and suburban schools (32.9%), and mid-poverty-level schools were less likely than were high-poverty-level schools to have replaced or upgraded HVAC systems (32.4% versus 48.8%). Substantial federal resources to improve ventilation in schools are available.§ Ensuring their use might reduce SARS-CoV-2 transmission in schools. Focusing support on schools least likely to have resource-intensive ventilation strategies might facilitate equitable implementation of ventilation improvements.
The influence of EGFR mutation status and PD-L1 expression in stage III unresectable non-small cell lung cancer treated with chemoradiation and consolidation durvalumab.
Authors: Udit Nindra, Samuel Xavier Stevens, Adel Shahnam, Abhijit Pal, Tamiem Adam, Po Yee Yip, Jenny HJ Lee, Michael J. Boyer, Adnan Nagrial, Steven Chuan-Hao Kao, Victoria Jane Bray
Journal: Journal of Clinical Oncology (2022)

e18810 Background: The PACIFIC trial established concurrent chemoradiation followed by one year of consolidation durvalumab as the standard of care for unresectable stage III non-small cell lung cancer (NSCLC). However, the data to support the use of durvalumab in patients with EGFR mutations and low PD-L1 expression is less clear. This study adds to the available evidence by describing the survival outcomes for patients with stage III unresectable NSCLC treated with chemoradiation followed by durvalumab with a focus on their EGFR mutation and PD-L1 status. Methods: This retrospective observational study was conducted at six sites across Sydney, Australia. It included patients diagnosed with unresectable stage III NSCLC treated with chemoradiation and at least one cycle of durvalumab between January 2018 to September 2021. Patients were stratified into EGFR wild-type and mutated tumours and PD-L1 tumour proportional score (TPS) greater than or less than 1%. Survival analyses were supplemented with cox proportional hazards regression models which estimated HRs for PFS in treatment group comparisons. The proportional hazards assumption was confirmed for all cox models. All statistical analysis was done using R version 4.1.1. Results: 146 patients were included in the analysis. The median follow-up from the start of Durvalumab was 15.1 months. The median age was 66 years in the EGFR mutated and 65 years in the EGFR wild-type cohorts. 61% (n = 89) of patients were male. 10% (n = 15) of patients had EGFR mutation. 42% (n = 61) of patients had a PD-L1 TPS of &lt; 1%. PD-L1 expression was similar in both cohorts with 47% (n = 7) of EGFR mutated patients having PD-L1 TPS of &lt; 1% compared with 45% (n = 59) in the wild-type group. The median progression-free survival (PFS) was 7.5 months for EGFR mutated patients versus 33.9 months for EGFR wild- type patients (HR: 2.7; 95% CI: 1.2 – 5.7; p = 0.01). There was no statistically significant difference in either PFS (HR 0.7, 95% CI 0.4 – 1.7, p = 0.43) or OS (HR 0.5, 95% CI 0.4 – 4.7, p = 0.16) for patients with PD-L1 TPS of &lt; 1% compared with PD-L1 TPS of &gt; 1%. Conclusions: Our data adds to the growing evidence that suggests consolidation durvalumab after definitive chemoradiation may not be as efficacious in patients with EGFR-mutated tumours. PD-L1 TPS did not affect survival outcomes.